In the conventional method of protection against disease by vaccination, the central principle involves the injection or ingestion of a material that will elicit antibodies against said material, such that when challenged alter with a pathogenic organism containing homologous material, the individual to whom the material has been administered is protected against the pathogenic disease. The material injected or ingested that have this property of eliciting antibodies are called antigens.
It has been known for many years that the immunogenicity (that is, its ability to elicit antibodies) of an antigen can be improved by the addition of so-called adjuvants. In some cases, materials that apparently have little or no immunogenicity have been made to make high titres of antibody in in vivo systems by the addition of an adjuvant. Some of these adjuvants re, however, highly toxic and can cause undesirable side effects or lesions. Aluminum hydroxide or aluminum phosphate are routinely used as adjuvant for human vaccines, but have been known to cause lumps at the site of injection. Freund's complete adjacent (FCA), a mixture of a light petroleum oil and killed Mycobacterium tuberculosis, can often produce excellent titres for materials which do not normally give antibodies in vivo under any other conditions. Unfortunately lesions will often develop at the site of injection when using this material, making the procedure unacceptable for human use.
There are a number of other materials which have been investigated for use as adjuvants. In published European patent Application No. 0149581, the use of muramyl di-peptide is disclosed. In published United Kingdom Patent Application No. 2,053,231, the use of a synthetic adjuvant consisting of tetrapeptides or pentapeptides is disclosed. In earlier patents, the use of oil emulsions is disclosed as having an adjuvanting effect. Unfortunately, it appears that the better a material is at behaving as an adjuvant to antigen immunogenicity, the worse are the side effects. For example, it has been shown that muramyl dipeptide is an excellent adjuvant but appears to have a number of undesirable properties which prevent its use in human vaccines.
In general, all the adjuvants presently in use in mammals fall into two distinct types. The first type involves the so-called "depot" effect and the second type depends on general immunological stimulation of the system under study. The adjuvants which rely on the depot effect are believed to bring the immune cells to the antigen site, where the depot effect relies on the injected antigen being trapped or insolubilized in a medium, giving sustained circulating levels. The second type of adjuvant, involving general stimulation of the immune system, appears to relay on an inflammatory reaction resulting in a series of cells being stimulated, such that any antigen has an improved chance of eliciting antibodies.
Current theories of immunology suggest that, in order to provide a potent antibody response, an antigen must be seen by both B cells, which subsequently develop into the antibody producing cells, and also by helper T-cells, which provide growth and differentiation signals to the antigen specific B-cells. Helper T-cells recognize the antigen on the surface of antigen-presenting cells (APC) in association with Class II major histomcompatibility complex (MHX) gene products.